Pharmacological Inhibition of c‐Jun N‐Terminal Kinase Activity Exacerbates Liver Damage in Schistosoma mansoni Infected Mice

Background and Aims Schistosomiasis is a neglected tropical disease affecting more than 250 million people worldwide. Eggs of the parasitic helminth S. mansoni cause major morbidity in the liver, spleen and intestine. Of note, egg‐released soluble antigens (SEA) induce the transcription factor c‐Jun in hepatocytes, promoting hepatocellular cell cycle activity, proliferation and apoptosis. In this study, we analysed the hepatic effect of pharmacological inhibition of c‐Jun N‐terminal kinase (JNK) after infection with S. mansoni . The JNK inhibitor SP600125 was chosen because it had no effect on schistosome viability. Methods Eight‐week‐old male mice were infected with 100 cercariae (♂ + ♀) and 6 weeks later treated with SP600125 via a subcutaneously implanted osmotic pump over 3 weeks. Hepatic damage, inflammation, fibrosis and metabolic aspects were analysed in liver and spleen tissue as well as in serum samples. Results JNK inhibitor‐treated mice infected with S. mansoni showed a parasite‐induced elevation of serum aminotransferases. Hepatic inflammation, the activation of hepatic stellate cells and metabolic exhaustion were observed in infected control mice. Additional SP600125 application almost doubled enhanced transaminases, hepatic cytokine expression, inflammation, necrosis, as well as HSC activation, and decreased glycogen stores to a minimum. Conclusions Our findings suggest a protective role of JNK/c‐Jun‐signalling in hepatic inflammation, hepatic stellate cell activation, and metabolic exhaustion during S. mansoni infection.